Mouse epidermal cell cultures have been utilized as a model for studying mechanisms of epithelial carcinogenesis in vitro. Such cells proliferate synchronously during the first 3 days in vitro. These cells can metabolize polycyclic hydrocarbon carcinogens with subsequent binding of activated products to cellular macromolecules. Epidermal cells respond to phorbol ester tumor promoters with a marked stimulation of proliferation. This response appears to be mediated through the polyamine biosynthetic pathway. Proliferation epidermis both in vitro and in vivo, including benign and malignant epidermal tumors appear to have a marked increase in the contractile protein, actin. Epidermal cells transformed in vitro proliferate at an increased rate grew in soft agar, have elevated fibrinolytic activity and produce tumors on injection back into animals. Vitamin A in the culture medium can inhibit epidermal proliferation, decrease carcinogen metabolism and decrease carcinogen binding to DNA. This retinoid also markedly increases epidermal glycoprotein synthesis.